Interferon Beta-Induced Restoration of Regulatory T-Cell Function in Multiple Sclerosis Is Prompted by an Increase in Newly Generated Naive Regulatory T Cells

Background: Naturally occurring regulatory T (T-reg) cells are functionally impaired in patients with relapsing-remitting multiple sclerosis. We recently showed that prevalences of newly generated CD31-coexpressing naive T-reg cells (recent thymic emigrant-T-reg cells) are critical for suppressive function of circulating T-reg cells, and a shift in the homeostatic composition of T-reg-cell subsets related to a reduced de novo generation of recent thymic emigrant-T-reg cells may contribute to the multiple sclerosis (MS)-related T-reg-cell dysfunction. Interferon beta, an immunomodulatory agent with established efficacy in MS, lowers relapse rates and slows disease progression. Emerging evidence suggests that T-reg-cell suppressive capacity may increase in patients with MS undergoing treatment with interferon beta, although the mechanisms mediating this effect are uncertain. Objective: To evaluate the effect of interferon beta treatment on the suppressive activity and the homeostasis of circulating T-reg cells in patients with MS. Participants: Twenty patients with relapsing-remitting MS and 18 healthy control subjects. Interventions: Administration of interferon beta. Main Outcome Measures: Effect of interferon beta on T-reg-cell homeostasis and suppressive capacity. Results: Suppressive capacities of T-reg cells were consistently upregulated at 3 and 6 months after treatment with interferon beta. The restoration of T-reg-cell function was paralleled by increased naive recent thymic emigrant-T-reg cells and a coincidental reduction in memory T-reg cells. Conclusion: The increase in T-reg-cell inhibitory capacity mediated by interferon beta treatment can be explained by its effect on the homeostatic balance within the T-reg cell compartment.